This invention relates to a method and apparatus for quantifying blood flow in tissue and specifically for quantifying blood flow in tissue at a location within the body where therapy or diagnosis is required. The ability to quantify tissue blood flow permits the physician to plan and schedule specific therapies designed for a patient""s particular condition. For example, blood flow is a carrier of therapeutic agents throughout the body. The ability to quantify blood flow at a site within the body where drug therapy is required will permit the physician to evaluate the extent to which therapeutic agents introduced into the circulatory system will actually reach and affect the site to be treated.
One clinical area in which the current invention is useful is in the treatment of cancer, particularly those cancer cases that are treated non-surgically. Almost all cancers treated non-surgically will undergo therapies whose efficacy is strongly related to tissue and tumor blood flow. A number of anti-cancer agents depend on the circulatory system for delivery to the target tissue. Blood flow, the carrier of therapeutic agents to the tumor, also acts as a carrier of oxygen. Increased blood supply increases tissue oxygenation and the concentration of chemotherapeutic agents. Correspondingly, the concentration of oxygen at the site and the concentration of chemotherapeutic agents are enhancers of the effectiveness of therapies such as radiation therapy and chemotherapy.
In the treatment of tumors, various techniques have been used to increase the blood flow and thereby increase the oxygen supply to the site in the tumor being treated. Efforts to increase blood flow to tumors include the use of vasoactive drugs, viscosity modifiers and local hyperthermia therapy. In these attempts, circulation is affected systemically but there is always a question of the extent to which circulation in the specific site to be treated is affected. The need to increase blood flow to diseased tissue is associated with a corresponding need to measure or quantify blood flow at the treatment site.
While the overall importance of blood flow to human health has long been recognized, techniques to quantify blood flow generally have not lent themselves to routine clinical application. Accordingly, it is a purpose of this invention to provide a method and apparatus that will measure blood flow at a specific location critical to patient treatment and permit convenient, routine clinical application.
Certain patient therapies involve the extraction for testing of a tissue sample or biopsy from a region of the body suspected of disease or known to be diseased. The extracted sample is examined to obtain a diagnosis or to assess treatment and, if the tissue is diseased, a treatment protocol is established. It is advantageous to determine the blood perfusion of tissue at the location of the biopsy (i.e.: at the site to be treated) so that the treatment protocol can be based on actual blood flow to the site. The device of this invention is useful in any clinical situation for which perfusion is of interest when a biopsy is being taken. Such situations include eschemic disease and organ failures such as kidney or liver failure. A typical cancer therapy protocol involves the treatment of diseased tissue by chemotherapy, hyperthermia and/or radiation, all of which are, in part, dependent on blood flow. In some cases the perfusion data is used to distinguish viable tissue from necrotic tissue. In other cases there may be within viable tissue a range of perfusion values which may guide the choice of the biopsy site.
In cancer cases the efficacy of almost all non-surgical therapies is strongly related to tissue and tumor blood flow. Blood flow is the carrier of chemotherapeutic agents to the tumor, the carrier of oxygen which contributes to the efficiency of oxic anti-cancer drugs, the primary mechanism of heat removal from tissue in hyperthermic treatment of tumors and the principal modulator of oxygenation which contributes to-the effectiveness of radiotherapy. The level of blood flow in a tumor is thought to correlate with probable therapy outcome. This allows individual planning of patient therapy strategies based on the basal level of tumor blood flow and the response to blood flow modifying agents.
The technique of the present invention involves a minimally invasive system for producing a signal characteristic of blood perfusion, measuring blood perfusion in tissue at a selected tissue biopsy site, and obtaining a biopsy sample at or near the site where blood perfusion is measured. Preferred embodiments include a signal producing device that introduces into tissue a signal producing agent and a system for receiving and processing a signal resulting from the action of the signal producing agent in the tissue.
One perfusion monitor using a thermal transducer based perfusion sensor and useful in the practice of this invention is disclosed in U.S. Pat. No. 4,852,027 issued to H. Frederick Bowman et al. Monitors with other perfusion sensors can be used, for example monitors with laser Doppler sensors, hydrogen clearance sensors or ultrasound. The perfusion sensor is mounted on a biopsy needle or other biopsy extraction probe so that tissue samples are taken from the region interrogated by the perfusion sensor. When the instrument is operated the extraction probe is inserted into the tissue to be interrogated, perfusion data is taken and then the probe is operated to extract a sample of the tissue interrogated by the perfusion sensor. In this manner perfusion data taken relates directly to the tissue extracted. The physician is not required to rely upon a generalized systematic tissue perfusion value for the patient from which perfusion at the site of the biopsy is inferred.
The instrument of this invention enables the physician to extract a biopsy sample and measure perfusion simultaneously in one procedure. The tissue forming the biopsy sample is tissue interrogated by the perfusion measurement device. The biopsy sample is extracted from tissue known to be perfused. Tissue perfusion is a strong (typically conclusive) indicator of tissue viability. Thus, the patient (or site) pathology can be determined from the extracted biopsy sample. This eliminates the need for two or multiple invasive procedures in order to obtain a perfused (i.e.: viable) biopsy sample, thus saving patient trauma and time.
The present invention provides: quantification of tissue perfusion to assist in formulating patient specific treatment strategies; the ability to augment the perfusion of specific tissue with blood flow modifying agents and to quantify the augmented perfusion; direct correlation of local tissue perfusion with histological analysis; the knowledge that tissue biopsy is being taken from non-necrotic tissue; and minimization of the number of biopsy probe insertions, thereby minimizing tissue trauma during the biopsy process. Further, because apparent or measured tissue perfusion is higher in tissue which comprehends major blood vessels within the interrogation volume, the device of this invention can be used to detect proximity to major vessels as the probe is being inserted to enable the practitioner to navigate a path through tissue which avoids unwanted puncture of blood vessels.